G J Williams1, A Lee, J C Craig. 1. Centre for Kidney Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia, 2145. gabrieW4@chw.edu.au
Abstract
BACKGROUND: Acute urinary tract infection (UTI) is common in children. By the age of seven years, 8.4% of girls and 1.7% of boys will have suffered at least one episode. Symptoms are systemic rather than localised in early childhood and consist of fever, lethargy, anorexia, and vomiting. UTI is caused by E. coli in over 80% of cases and treatment consists of a course of antibiotics. Due to the unpleasant acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term antibiotics aimed at preventing recurrence. However these medications may cause side effects and promote the development of resistant bacteria. OBJECTIVES: To determine the efficacy and side effects of long-term antibiotics given to prevent recurrent UTI in children. SEARCH STRATEGY: A search of MEDLINE (1966 to Jan 2001), EMBASE (1988 to Jan 2001) and the Cochrane Controlled Trials Register for relevant randomised controlled trials without language restriction; reference lists of review articles; contact with content experts. SELECTION CRITERIA: Randomised comparisons of two or more antibiotics and placebo with one or more antibiotics to prevent recurrent UTI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted information. For each trial, information was collected on the methods of the trial, participants, interventions and outcomes. A random-effects model was used to estimate a summary relative risk (RR) and a summary risk difference (RD) for recurrent UTI. Heterogeneity tests and subgroup analyses were carried out based on a priori hypothesis of plausible effect modification. MAIN RESULTS: There were three trials (n = 151) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied among the studies (10 weeks to 12 months). The method of allocation concealment in the three trials was inadequate, unclear and adequate. The overall rate of recurrent UTI in the placebo/no treatment group was 63% (48/76). Compared to placebo/no treatment, antibiotics reduced the risk of recurrent UTI (RR 0.36, 95% CI 0.16 to 0.77; RD -46%, 95% CI -59% to -33%). No side effects were described in any of these three trials. There was one double-blinded trial (n = 120) with unclear allocation concealment that compared two different types of antibiotics to prevent recurrent UTI. Nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a six month period (RR 0.48, 95% CI 0.25 to 0.92; RD -18%, 95% CI -34% to -3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) than patients receiving trimethoprim (RR 3.17, 95% CI 1.36 to 7.37; RD 22%, 95% CI 8% to 36%). REVIEWER'S CONCLUSIONS: Most published studies to date have been poorly designed with biases known to overestimate the true treatment effect. Large, properly randomised, double blinded trials are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.
BACKGROUND: Acute urinary tract infection (UTI) is common in children. By the age of seven years, 8.4% of girls and 1.7% of boys will have suffered at least one episode. Symptoms are systemic rather than localised in early childhood and consist of fever, lethargy, anorexia, and vomiting. UTI is caused by E. coli in over 80% of cases and treatment consists of a course of antibiotics. Due to the unpleasant acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term antibiotics aimed at preventing recurrence. However these medications may cause side effects and promote the development of resistant bacteria. OBJECTIVES: To determine the efficacy and side effects of long-term antibiotics given to prevent recurrent UTI in children. SEARCH STRATEGY: A search of MEDLINE (1966 to Jan 2001), EMBASE (1988 to Jan 2001) and the Cochrane Controlled Trials Register for relevant randomised controlled trials without language restriction; reference lists of review articles; contact with content experts. SELECTION CRITERIA: Randomised comparisons of two or more antibiotics and placebo with one or more antibiotics to prevent recurrent UTI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed and extracted information. For each trial, information was collected on the methods of the trial, participants, interventions and outcomes. A random-effects model was used to estimate a summary relative risk (RR) and a summary risk difference (RD) for recurrent UTI. Heterogeneity tests and subgroup analyses were carried out based on a priori hypothesis of plausible effect modification. MAIN RESULTS: There were three trials (n = 151) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied among the studies (10 weeks to 12 months). The method of allocation concealment in the three trials was inadequate, unclear and adequate. The overall rate of recurrent UTI in the placebo/no treatment group was 63% (48/76). Compared to placebo/no treatment, antibiotics reduced the risk of recurrent UTI (RR 0.36, 95% CI 0.16 to 0.77; RD -46%, 95% CI -59% to -33%). No side effects were described in any of these three trials. There was one double-blinded trial (n = 120) with unclear allocation concealment that compared two different types of antibiotics to prevent recurrent UTI. Nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a six month period (RR 0.48, 95% CI 0.25 to 0.92; RD -18%, 95% CI -34% to -3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) than patients receiving trimethoprim (RR 3.17, 95% CI 1.36 to 7.37; RD 22%, 95% CI 8% to 36%). REVIEWER'S CONCLUSIONS: Most published studies to date have been poorly designed with biases known to overestimate the true treatment effect. Large, properly randomised, double blinded trials are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.